JACC: Clinical Electrophysiology
Volume 4, Issue 9, September 2018 DOI: 10.1016/j.jacep.2018.05.007
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Focus on Ventricular Arrhythmias and Cardiomyopathy

Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in Nonischemic Heart Disease
An International Ventricular Tachycardia Ablation Center Collaborative Study

Marmar Vaseghi, Tiffany Y. Hu, Roderick Tung, Pasquale Vergara, David S. Frankel, Luigi Di Biase, Usha B. Tedrow, Jeffrey A. Gornbein, Ricky Yu, Nilesh Mathuria, Shiro Nakahara, Wendy S. Tzou, William H. Sauer, J. David Burkhardt, Venkatakrishna N. Tholakanahalli, Timm-Michael Dickfeld, J. Peter Weiss, T. Jared Bunch, Madhu Reddy, David J. Callans, Dhanunjaya R. Lakkireddy, Andrea Natale, Francis E. Marchlinski, William G. Stevenson, Paolo Della Bella and Kalyanam Shivkumar

Author + information

vol. 4 no. 9 1141-1150
DOI: 
https://doi.org/10.1016/j.jacep.2018.05.007
Published By: 
JACC: Clinical Electrophysiology
Print ISSN: 
2405-5018
Online ISSN: 
2405-500X
History: 
  • Received March 2, 2018
  • Revision received May 2, 2018
  • Accepted May 15, 2018
  • Published online September 17, 2018.

Article Versions

Copyright & Usage: 
2018 American College of Cardiology Foundation

Author Information

  1. Marmar Vaseghi, MD, PhDa,∗∗ (mvaseghi{at}mednet.ucla.edu),
  2. Tiffany Y. Hu, MDa,∗,
  3. Roderick Tung, MDb,
  4. Pasquale Vergara, MD, PhDc,
  5. David S. Frankel, MDd,
  6. Luigi Di Biase, MD, PhDe,
  7. Usha B. Tedrow, MDf,
  8. Jeffrey A. Gornbein, DrPHg,
  9. Ricky Yu, MDa,
  10. Nilesh Mathuria, MDh,
  11. Shiro Nakahara, MD, PhDi,
  12. Wendy S. Tzou, MDj,
  13. William H. Sauer, MDj,
  14. J. David Burkhardt, MDk,
  15. Venkatakrishna N. Tholakanahalli, MDl,
  16. Timm-Michael Dickfeld, MD, PhDm,
  17. J. Peter Weiss, MD, MScn,
  18. T. Jared Bunch, MDn,
  19. Madhu Reddy, MDo,
  20. David J. Callans, MDd,
  21. Dhanunjaya R. Lakkireddy, MDp,
  22. Andrea Natale, MDk,
  23. Francis E. Marchlinski, MDd,
  24. William G. Stevenson, MDq,
  25. Paolo Della Bella, MDc and
  26. Kalyanam Shivkumar, MD, PhDa
  1. aUCLA Cardiac Arrhythmia Center, UCLA Health System, Los Angeles, California
  2. bUniversity of Chicago, Chicago, Illinois
  3. cHospital San Raffaele, Milan, Italy
  4. dHospital of the University of Pennsylvania; Philadelphia, Pennsylvania
  5. eAlbert Einstein College of Medicine at Montefiore Hospital, Bronx, New York
  6. fBrigham and Women’s Hospital, Boston, Massachusetts
  7. gDepartment of Biostatistics, University of California, Los Angeles, Los Angeles, California
  8. hBaylor St. Luke’s Medical Center/Texas Heart Institute, Houston, Texas
  9. iDokkyo Medical University Koshigaya Hospital, Saitama, Japan
  10. jUniversity of Colorado, Aurora, Colorado
  11. kTexas Cardiac Arrhythmia Institute, St. David’s Medical Center; Austin, Texas
  12. lUniversity of Minnesota Medical Center, Minneapolis VA Medical Center, Minneapolis, Minnesota
  13. mUniversity of Maryland Medical Center, Baltimore, Maryland
  14. nIntermountain Heart Institute, Intermountain Medical Center, Murray, Utah
  15. oUniversity of Kansas Medical Center, Kansas City, Kansas
  16. pOverland Park Regional Medical Center, HCA Midwest Health, Overland Park, Kansas City, Kansas
  17. qVanderbilt University, Nashville, Tennessee
  1. ↵∗Address for correspondence:
    Dr. Marmar Vaseghi, UCLA Cardiac Arrhythmia Center, 100 Medical Plaza, Suite 660, Los Angeles, California 90095.

Abstract

Objectives This study sought to characterize ventricular tachycardia (VT) ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust these outcomes by patient-related comorbidities that could explain differences in arrhythmia recurrence rates.

Background Outcomes of catheter ablation of VT in patients with NICM could be related to etiology of NICM.

Methods Data from 2,075 patients with structural heart disease referred for catheter ablation of VT from 12 international centers was retrospectively analyzed. Patient characteristics and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox proportional hazards modeling was used to adjust for potential confounders.

Results Of 780 NICM patients (57 ± 14 years of age, 18% women, left ventricular ejection fraction 37 ± 13%), underlying prevalence was 66% for dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year freedom from VT was 69%, and freedom from VT, heart transplantation, and death was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated superior VT-free survival (82%) versus DICM (p ≤ 0.01). Valvular cardiomyopathy had the poorest unadjusted VT-free survival, at 47% (p < 0.01). After adjusting for comorbidities, including age, heart failure severity, ejection fraction, prior ablation, and antiarrhythmic medication use, myocarditis, ARVC, and DICM demonstrated similar outcomes, whereas hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis had the highest risk of VT recurrence.

Conclusions Catheter ablation of VT in NICM is effective. Etiology of NICM is a significant predictor of outcomes, with ARVC, myocarditis, and DICM having similar but superior outcomes to hypertrophic cardiomyopathy, valvular cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

Key Words

Catheter ablation of ventricular tachycardia (VT) in patients with nonischemic cardiomyopathy (NICM) has been reported to have less favorable outcomes and higher VT recurrence rates as compared with patients with ischemic cardiomyopathy (ICM) (1–3). However, NICM can result from a wide-spectrum of disease processes, and the differences in outcomes may be driven by the etiology of NICM. Single-center studies have suggested differential outcomes for patients with various types of NICM, with arrhythmogenic right ventricular cardiomyopathy (ARVC) often reported to have the most favorable and sarcoidosis reported to have relatively poorer outcomes (4,5). However, single-center studies are limited by small numbers of patients. Further, the differences in outcomes observed of various etiologies could also be driven by patient comorbidities. The aim of this study was to use a large international registry of VT ablation patients to evaluate outcomes of NICM by etiology and to adjust these outcomes for significant comorbidities that may be driving the underlying arrhythmia success and recurrence rates. These data not only are important for prognosis and discussion of benefits and outcomes with patients, but also can be used to better understand substrates that underlie etiologies with less successful outcomes.

Methods

Data collection

Data were collected by the International Ventricular Tachycardia Ablation Center Collaborative from 12 international referral centers, as has been previously described (6), and included 2,218 patients with structural heart disease who underwent catheter ablation for VT. Patients with known etiology of NICM who underwent VT ablation between 2002 and 2014 were included. Data from a total of 780 patients with NICM and an identified etiology in the database were retrospectively analyzed. Patients with mixed cardiomyopathy (ICM and NICM) were excluded from the analysis. Patients with dilated idiopathic cardiomyopathy (DICM) were used as reference. The 6 most common etiologies were used for analysis and included DICM with ejection fraction <50%, arrhythmogenic ventricular cardiomyopathy, myocarditis, cardiac sarcoidosis, hypertrophic cardiomyopathy (HCM), and valvular cardiomyopathy. Valvular cardiomyopathy was defined as severe regurgitation or stenosis of any valve or history of valvular replacement due to severe valvular regurgitation or stenosis. All centers were contacted and confirmed etiologies of cardiomyopathy based on their institutional database and specific review of patient data records. The Institutional Review Boards of each participating center approved collection of the data.

Electrophysiology study and ablation

The primary strategy for VT ablation across centers was substrate-based modification of scar guided by electroanatomic mapping. Electroanatomic mapping was performed using CARTO (Biosense Webster, Diamond Bar, California) or NAVX (St. Jude Medical/Abbott, St. Paul, Minnesota) with standard low-voltage settings (<1.5 mV) (6). Procedures were performed under conscious sedation or general anesthesia. VT was induced with programmed stimulation using up to 2 sites, 2 drive drains, and up to 3 extrastimuli as previously described (7). The clinical VTs followed by nonclinical VTs were targeted for ablation. If VT was hemodynamically tolerated, activation and entrainment mapping was performed (8). Pace mapping was used to target potential VT exit sites, where matches with the targeted VT were observed (9). Regions of late activation or local conduction delay as evidenced by split, fractionated, or isolated late potentials were tagged and targeted for ablation (10,11). Elimination of sustained monomorphic VT inducibility served as the common desired procedural endpoint and programmed stimulation was performed after ablation unless hemodynamic instability or procedural duration was prohibitive (12).

Percutaneous epicardial mapping and ablation was performed at the discretion of the operator. If percutaneous epicardial access was limited by prior cardiac surgery or adhesions, the epicardium was accessed surgically. Radiofrequency catheter ablation of VT was performed using nonirrigated catheters (Navi-Star, Biosense Webster), open-irrigated catheters (ThermoCool, ThermoCool SF, or Navistar RMT 3.5 mm, Biosense Webster), or closed-loop irrigated catheters (Chilli, Boston Scientific, Marlborough, Massachusetts). Electroanatomic mapping was performed using CARTO (Biosense Webster) or NAVX (St. Jude Medical/Abbott).

Follow-up

In patients who underwent multiple ablations, data from the most recent ablation were considered for follow-up and the date of ablation was used as the beginning of follow-up. Follow-up for VT recurrence included office visits and device interrogations if a device was present. Endpoints included VT recurrence and composite outcome of VT recurrence, death, or orthotopic heart transplant (OHT). VT recurrence was defined as documented sustained VT (≥30 s) or any appropriate implantable cardioverter-defibrillator therapy, including antitachycardia pacing.

Statistical analysis

Continuous data are reported as mean ± SD and compared across etiology groups using a 1-way analysis of variance model. Categorical variables are reported as percentages or frequencies. Comparison of categorical variables across etiology groups was performed using Fisher exact test. Age across etiologies was compared using a 1-way analysis of variance. Ordinal New York Heart Association (NYHA) functional class values across groups were compared using the nonparametric Kruskal-Wallis test, as NYHA functional classes did not follow a normal distribution.

Event-free survival curves were computed using the Kaplan-Meier method and compared across the 6 etiologies using the Cox proportional hazards model. An attempt was made to control for the following confounders (primary: age, sex, NYHA functional class, VT storm; secondary: chronic kidney disease, diabetes mellitus, left ventricular ejection fraction [LVEF], VT ablation center, having previously failed 2 or more antiarrhythmic agents, prior VT ablation, atrial fibrillation, hypertension, need for epicardial ablation, and interactions of LVEF with HCM and ARVC) by adding them to the Cox model. The backward stepwise method with a p ≤ 0.05 variable retention criterion was used to determine what subset of 15 potential confounders should be retained in the model, controlling for NICM etiology. A model using only the 4 primary potential confounders and NICM etiologies was also evaluated. Model accuracy was quantified using the Harrell C-statistic.

Competing risks of VT recurrence and death or transplant incidence were similarly computed using the method of Gray (13) and compared across the 6 NICM etiologies using the corresponding Fine and Gray competing risk model, controlling for non–VT-related death or heart transplantation. A similar backward stepwise method under this model was used to determine which of the 12 potential confounders to retain and for evaluating a model with only etiology and the 4 primary potential confounders included.

The hazard ratio (HR) and its corresponding 95% confidence interval (CI) are reported for the Cox or Fine and Gray models. Reported p values were adjusted for multiple comparisons using the Tukey test when appropriate. Analysis was performed using R software version 3.4 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Patient and procedural characteristics

Between 2002 and 2014, 780 patients (57 ± 14 years of age, 18% women, LVEF 37 ± 13%) with the 6 most common reported NICM etiologies in the database were identified. Underlying NICM etiologies were as follows: DICM in 518 (66%), ARVC in 100 (13%), valvular in 50 (6%), myocarditis in 50 (6%), HCM in 35 (4%), and sarcoidosis in 27 (3%). Patient characteristics by etiologies are shown in Table 1. Prior ablation had been performed in 325 (45%) patients. An implantable cardioverter-defibrillator was present in 588 (80%) patients at time of ablation.

View this table:
Table 1

Patient Characteristics by Etiology

Epicardial mapping was performed in 49% and epicardial ablation was performed in 38%. Acute procedural success, defined as VT no longer being inducible, was achieved in 436 (65%) patients. Procedural characteristics by etiology are shown in Table 2. Overall complication rates of ablation were not statistically different among different etiologies (Table 2). Type of complication by etiology is reported in Online Tables 1 and 2.

View this table:
Table 2

Procedural Characteristics by Etiology

Patient outcomes

At 1-year post-ablation, 69% of the 780 patients with NICM were free from VT recurrence and 62% were free from the composite outcome of VT recurrence, death, and OHT (Figure 1). Median follow-up was 12.8 (interquartile range: 4.0 to 26.0) months. At the end of follow up, VT recurred in 318 (41%) patients, death occurred in 137 (18%) patients, and 47 (6%) patients underwent cardiac transplantation. Incidence of death and transplantation is shown in Online Figure 1. In 78 (10%) patients, death or cardiac transplantation occurred without VT recurrence. Kaplan-Meier curves for VT recurrence are shown in Figure 2. In the Gray or Kaplan-Meier analysis, sarcoidosis and valvular cardiomyopathy had the highest VT recurrence rates (50% and 43%, respectively) at 1 year whereas myocarditis and ARVC had the best unadjusted outcomes, with a VT recurrence rate of 23% and 17% at 1 year, respectively (p < 0.01 compared with DICM) (Figure 2). VT recurrence rate at 1 year for DICM was 32% whereas for HCM it was 38%. Unadjusted Kaplan-Meier analysis also demonstrated higher VT- or transplant-free survival for patients with ARVC and myocarditis (82% and 75%, respectively); outcomes that were superior at 1 year to valvular cardiomyopathy (47%) and sarcoidosis (50%) (Figure 3). Freedom from VT recurrence, death, or OHT was 59% for DICM and 56% for HCM.

Figure 1
Figure 1

Competing Risk Analysis for the Overall Nonischemic Cardiomyopathy Population

Freedom from ventricular tachycardia (VT) at follow-up was 32% whereas the freedom from any event, including VT, death, and cardiac transplantation was 60% in the overall population of nonischemic cardiomyopathy patients. OHT = orthotopic heart transplant.

Figure 2
Figure 2

Unadjusted VT Recurrence Rates by Etiology

Sarcoidosis and valvular cardiomyopathy have the highest rates of ventricular tachycardia (VT) recurrence at 1 year.

Figure 3
Figure 3

Unadjusted Incidence of VT, Death, and Cardiac Transplantation

Incidence of VT recurrence, death, and cardiac transplantation at 1 year was higher for sarcoidosis, valvular cardiomyopathy, and HCM patients and lower for those with ARVC and myocarditis. Abbreviations as in Figure 2.

On multivariable analysis, significant variables for VT recurrence included age, LVEF, use of 2 or more antiarrhythmic medications, prior VT ablation, and number of induced VTs in addition to etiology of cardiomyopathy. After adjusting for these variables and ablation center, VT storm, chronic kidney disease, and epicardial ablation, which were significant on univariable analysis, were not significant for VT recurrence or the combined endpoint on multivariable analysis. After adjusting for age, LVEF, center, use of 2 or more antiarrhythmic medications, prior VT ablation, and number of induced VTs, ARVC and myocarditis were associated with a similar risk of VT recurrence as DICM (HR: 1.07 [95% CI: 0.65 to 1.78] and HR: 1.05 [95% CI: 0.54 to 2.02], respectively) (Figures 4 and 5). On the other hand, sarcoidosis had the highest risk of VT recurrence (HR: 1.97 [95% CI: 1.09 to 3.55]) followed by HCM (HR: 1.88 [95% CI: 1.08 to 3.26]) and valvular cardiomyopathy (HR: 1.7 [95% CI: 1.04 to 2.77]). Similarly, in multivariable analysis adjusting for the previously mentioned variables, ARVC and myocarditis had similar risk for combined endpoint of VT recurrence, death, and transplantation (HR: 1.00 [95% CI: 0.61 to 1.64] and HR: 1.07 [0.60 to 1.93], respectively) (Figures 4 and 6) compared with DICM. In contrast, after adjusting for confounders including age, NYHA functional class, LVEF, ablation center, prior VT ablation, number of antiarrhythmic medication and number of induced VTs, valvular cardiomyopathy (HR: 1.73 [95% CI: 1.14 to 2.62]) and HCM (HR: 1.81 [95% CI: 1.07 to 3.07]) had the highest HRs for the combined endpoint of VT, death, and cardiac transplantation (Figure 6). Other factors independently associated with less favorable combined outcomes included age, lower LVEF, NYHA functional class, use of 2 or more antiarrhythmic medications, prior VT ablation, and number of induced VTs (Figures 5 and 6). NYHA functional class had a hazard ratio of 1.32 (p < 0.01) for the combined endpoint but was not significant for VT recurrence alone, after adjusting for LVEF.

Figure 4
Figure 4

Adjusted VT Recurrence and Adjusted VT Recurrence, Death, and Transplantation by NICM Etiology

(A) Adjusted ventricular tachycardia (VT) recurrence rates by etiology and (B) adjusted combined endpoint of VT recurrence, death, and transplantation by etiology are shown. Valvular cardiomyopathy, hypertrophic cardiomyopathy (HCM), and sarcoidosis have the least favorable outcomes compared with dilated idiopathic cardiomyopathy (DICM). There is no difference in the adjusted outcomes of arrhythmogenic right ventricular cardiomyopathy (ARVC) and myocarditis as compared with DICM.

Figure 5
Figure 5

Characteristics Associated With VT Recurrence

Multivariable Cox proportional hazards ratio plot for VT recurrence demonstrates that sarcoidosis, HCM, and valvular cardiomyopathy are independently associated with higher risk of VT recurrence after adjusting for other comorbidities. Age, multiple antiarrhythmic drug (AAD) use, prior VT ablation, and greater number of induced VTs were also associated with increased risk, whereas a higher left ventricular ejection fraction (LVEF) was associated with a lower risk of recurrence. DICM was used as reference for etiologies. *Adjusted for LVEF interactions with etiology of cardiomyopathy such as ARVC, variable represents the hazard ratio for every 5% increase in LVEF. CI = confidence interval; NYHA = New York Heart Association; other abbreviations as in Figure 2.

Figure 6
Figure 6

Characteristics Associated With VT-Free Transplant-Free Survival

Multivariable Cox proportional hazards ratio plot for VT recurrence, death, and cardiac transplantation demonstrates that HCM and valvular cardiomyopathy are independently associated with poorer outcomes after adjusting for other comorbidities. Sarcoidosis had a high hazard ratio but did not reach statistical significance. Age, multiple AAD use, NYHA functional class, prior VT ablation, and greater number of induced VTs were also associated with a poorer combined endpoint, whereas higher LVEF conferred a VT-free survival benefit. ARVC and myocarditis had similar risk for the combined endpoint compared to DICM. DICM was used as reference for etiologies. *Adjusted for LVEF interactions with etiology of cardiomyopathy such as ARVC, variable represents the hazard ratio for every 5% increase in LVEF. Abl = ablation; OHT = orthotopic heart transplant; other abbreviations as in Figures 2 and 4.

Discussion

Major findings

In this large multicenter study, outcomes of various NICM etiologies were evaluated. This is the largest study to report VT ablation outcomes in patients with valvular heart disease, myocarditis, and HCM. We show that success rates for VT ablation are driven by certain etiologies in NICM, whereas in other etiologies, additional patient characteristics contribute to the observed outcomes. Having a sufficient number of patients allowed us to be able to adjust for comorbidities, and we were able to show that DICM had a similar risk of VT recurrence and VT recurrence, transplantation, and death compared with ARVC and myocarditis. Sarcoidosis, HCM, and valvular cardiomyopathy had the highest risk for VT recurrence, whereas valvular cardiomyopathy and HCM had the highest risk for the combined endpoint of cardiac transplantation and death. Furthermore, despite having normal LVEFs, the adjusted outcomes in patients with HCM are relatively poor as compared with DICM.

VT ablation in NICM

VT ablation decreases VT recurrence in patients presenting with implantable cardioverter-defibrillator shocks and VT (14–16). It has been further reported that lack of VT recurrence after ablation is associated with improved mortality regardless of NYHA functional class in those with moderate to severe systolic dysfunction (7). In this multicenter study of NICM patients, 69% were free of VT at 1-year of follow-up, whereas freedom from VT, death, and cardiac transplantation was 62% at 1 year. These results are similar to those previously reported in single-center studies with 1-year VT-free survival rates ranging from 60% to 77% (3,5,17,18).

NICM patients with VT are reported to have less favorable outcomes after catheter ablation as compared with ICM patients. The HELP-VT (Heart Centre of Leipzig VT) study, which prospectively compared dilated cardiomyopathy with ICM outcomes, reported a poorer VT-free survival at 1 year for dilated cardiomyopathy of 40.5% versus 57.0% for ICM patients (1). Tung et al. (7) reported that 77% of ICM patients in the International Ventricular Tachycardia Ablation Center Collaborative registry were free of VT recurrence at 1 year, which was also higher than the VT-free survival rate observed in the NICM population at 1 year. It is possible that the less favorable outcomes in the setting of NICM are partially driven by the heterogeneity in etiology (5,17,19). In a single-center study, Tokuda et al. (5) reported that patients with ARVC had better outcomes after catheter ablation of VT as compared with DICM patients, whereas patients with sarcoidosis appeared to have the poorest VT-free survival rates. Santangeli et al. (20) reported favorable success rates for VT ablation in ARVC, with 71% VT-free survival at 4.7-year follow-up. Della Bella et al. (17) reported a 39% recurrence rate for DICM patients after catheter ablation as compared with 31% for patients with ARVC and 25% for HCM patients, though in this series only 5 patients had HCM and only 13 had ARVC (17). On the other hand, in another single-center study of 166 patients, which included 20 ARVC patients, Maury et al. (4) observed similar VT recurrence rates for patients with DICM as compared with ARVC. Of note, these studies did not adjust for potential confounders that could explain the differences in outcomes of various etiologies observed. Important factors known to influence outcomes include age, NYHA functional class, and VT storm (1,3–5).

In this large multicenter study of NICM patients, sarcoidosis, valvular cardiomyopathy, and HCM had the least favorable outcomes for VT recurrence and valvular cardiomyopathy and HCM had the poorest VT recurrence, cardiac transplantation, and death outcomes, even after adjusting for potential confounders including age, NYHA functional class, and history of VT storm. HCM was also associated with high risk of recurrence, transplantation, and death as compared with DICM. However, we found that after adjusting for comorbidities, DICM had similar outcomes to ARVC and myocarditis. It is interesting to note that after adjusting for other variables, including etiology of cardiomyopathy, prior VT ablation, LVEF, and number of induced VTs and antiarrhythmic medications, VT storm was no longer significant in the multivariable analysis for outcomes, whereas NYHA functional class remained an independent predictor of the combined endpoint.

Influence of the substrate

In this study, sarcoidosis, valvular cardiomyopathy, and HCM were associated with a higher risk of VT recurrence. The relatively higher risk for VT recurrence in these etiologies may be driven by scar location. Although in this retrospective registry, the location of scar, as observed on imaging and electroanatomic data, was not specifically collected, it may explain the poorer outcomes seen with certain etiologies. Sarcoidosis and HCM patients often harbor septal scars, which can be difficult to access from either the endocardium or the epicardium (21,22). Furthermore, it is possible that scar and disease progression play an important role in sarcoidosis, if untreated or refractory to immunosuppressive therapy. In this more challenging population, other adjunctive therapies such as arterial or venous alcohol ablation, surgical cryoablation, bipolar ablation, or coiling if the coronary anatomy is suitable have been used to address septal and midmyocardial scars (23–27). Valvular cardiomyopathy, in addition to presenting with potentially limited access due to mechanical valves or prior surgical pericardial adhesions, may present with basal scars, which, given both the thickness of the ventricle and overlying epicardial fat in this region (28,29), can pose a challenge to ablation. In contrast, both myocarditis and ARVC tend to have an epicardial substrate with better targets for ablation, including late potentials and fractionated electrograms (20,30–34), potentially leading to improved outcomes.

Finally, the number of patients with HCM, valvular cardiomyopathy, and sarcoidosis was smaller than those with DICM and ARVC. Although the location of scars might have led to the poorer outcomes noted with HCM, valvular cardiomyopathy, and sarcoidosis, it is also possible that less experience with these substrates as compared with ARVC or DICM partially contributed to the outcomes observed.

Study limitations

The present study is retrospective and represents outcomes reported at specialized VT ablation centers. The results, therefore, may not be applicable to all institutions. Etiology of cardiomyopathy was based on that reported in the database and identified by each center based on imaging data (magnetic resonance imaging and cardiac positron emission tomography), viral serology, and patient history. It is possible that work-up of the etiology of cardiomyopathy might have been variable at different institutions or that there may have been overlap of etiologies that limited the conclusions of this study. In particular, sarcoidosis can be underdiagnosed or misclassified (35). However, any misclassification related to this would have biased the outcomes toward null. Therefore, our estimate of the differences in outcomes of sarcoidosis compared with DICM may represent a conservative estimate. Given retrospective collection of variables, the effect of certain procedural variables, including high-density multielectrode mapping catheters, could not be analyzed. Not all confounders could be evaluated in multivariable analysis, and therefore only those thought to have a significant effect on outcomes were included in a stepwise fashion.

Conclusions

Catheter ablation of VT in NICM is effective, but certain etiologies significantly have an impact on outcomes. Patients with ARVC and myocarditis had better outcomes after catheter ablation as compared with DICM patients; however, after adjusting for other confounders, these differences appear to be driven by comorbidities including age and NYHA functional class in DICM patients. Patients with sarcoidosis, valvular cardiomyopathy, and HCM were at the highest risk of VT recurrence after catheter ablation, even after adjusting for potential comorbidities.

Perspectives

COMPETENCY IN MEDICAL KNOWLEDGE: Catheter ablation of VT in NICM is effective, but characterization of outcomes can be confounded by an underlying heterogeneous disease process. In this study, etiology of NICM was a significant predictor of VT recurrence, death, and cardiac transplantation. Patients with ARVC, myocarditis, and DICM had similar but superior outcomes after catheter ablation of VT, compared with those with HCM, valvular cardiomyopathy, and sarcoidosis.

TRANSLATIONAL OUTLOOK: Better characterization of the substrate in NICM, such as valvular cardiomyopathy and sarcoidosis, could help inform both medical and procedural therapy and improve outcomes. Translational studies and specific models of NICM targeted at specific etiologies are needed to better understand pathophysiological changes that cause ventricular arrhythmias and affect outcomes after catheter ablation in this population.

Appendix

Online Tables 1 and 2 and Online Figure 1 [S2405500X18304006_mmc1.pdf]

Footnotes

  • ↵∗ Drs. Vaseghi and Hu contributed equally to this work and are joint first authors. Katia Zeppenfeld, MD, served as Guest Editor for this paper.

  • The study was an unfunded, investigator-initiated collaborative study. Dr. Vaseghi is supported by National Institutes of Health Grant No. DP2 DP2HL132356-01 and Dr. Shivkumar is supported by National Institutes of Health Grant No. OT2OD023848. Dr. Di Biase has served as a consultant for Stereotaxis, Boston Scientific, Abbott, and Biosense Webster; and has received speaker/travel honoraria from Medtronic, Atricure, Pfizer, EpiEP, and Biotronik. Dr. Tedrow has received honoraria from Medtronic, St. Jude Medical, and Boston Scientific; and research grant support from Biosense Webster and St. Jude Medical. Dr. Tzou has received speaker honoraria from Medtronic, Boston Scientific, and Biosense Webster; and has served as a consultant for Biosense Webster and Abbott. Dr. Burkhardt has received honoraria from Biosense Webster. Dr. Tholakanahalli has received research grant support from and owns intellectual property rights at St. Jude Medical. Dr. Dickfeld has received honoraria from Biosense Webster, Siemens, St. Jude Medical, Abbott Laboratories, and Impulse Dynamics USA; and research grant from GE Healthcare and Biosense Webster. Dr. Weiss has received consulting honoraria from Stereotaxis. Dr. Bunch has received honoraria from Boston Scientific. Dr. Reddy has received speakers’ honoraria from Pfizer, Zoll, Janssen, and BMS. Dr. Callans has received honoraria from Biosense Webster, Medtronic, and St. Jude Medical. Dr. Natale has served as a consultant for Biosense Webster, Stereotaxis, Abbott, and Boston Scientific; and has received speaker/travel honoraria from Medtronic, Atricure, Biotronik, and Janssen. Dr. Stevenson has received speakers’ honoria from Abbott Medical and Boston Scientific; and is co-holder of a patent for needle ablation that is consigned to Brigham and Women’s Hospital and co-held with Biosense Webster. Dr. Della Bella has received research grant support from Biosense Webster; and has served as a consultant for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

  • All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.

Abbreviations and Acronyms
ARVC
arrhythmogenic right ventricular cardiomyopathy
CI
confidence interval
DICM
dilated idiopathic cardiomyopathy
HCM
hypertrophic cardiomyopathy
HR
hazard ratio
ICM
ischemic cardiomyopathy
LVEF
left ventricular ejection fraction
NICM
nonischemic cardiomyopathy
NYHA
New York Heart Association
OHT
orthotopic heart transplant
VT
ventricular tachycardia
  • Received March 2, 2018.
  • Revision received May 2, 2018.
  • Accepted May 15, 2018.

References

  1. ↵
    1. Dinov B.,
    2. Fiedler L.,
    3. Schonbauer R.,
    4. et al.
    (2014) Outcomes in catheter ablation of ventricular tachycardia in dilated nonischemic cardiomyopathy compared with ischemic cardiomyopathy: results from the Prospective Heart Centre of Leipzig VT (HELP-VT) Study. Circulation 129:728–736.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Proietti R.,
    2. Essebag V.,
    3. Beardsall J.,
    4. et al.
    (2015) Substrate-guided ablation of haemodynamically tolerated and untolerated ventricular tachycardia in patients with structural heart disease: effect of cardiomyopathy type and acute success on long-term outcome. Europace 17:461–467.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Kumar S.,
    2. Romero J.,
    3. Mehta N.K.,
    4. et al.
    (2016) Long-term outcomes after catheter ablation of ventricular tachycardia in patients with and without structural heart disease. Heart Rhythm 13:1957–1963.
    OpenUrl
  4. ↵
    1. Maury P.,
    2. Baratto F.,
    3. Zeppenfeld K.,
    4. et al.
    (2014) Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%. Eur Heart J 35:1479–1485.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Tokuda M.,
    2. Tedrow U.B.,
    3. Kojodjojo P.,
    4. et al.
    (2012) Catheter ablation of ventricular tachycardia in nonischemic heart disease. Circ Arrhythm Electrophysiol 5:992–1000.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Marchlinski F.E.,
    2. Callans D.J.,
    3. Gottlieb C.D.,
    4. Zado E.
    (2000) Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation 101:1288–1296.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Tung R.,
    2. Vaseghi M.,
    3. Frankel D.S.,
    4. et al.
    (2015) Freedom from recurrent ventricular tachycardia after catheter ablation is associated with improved survival in patients with structural heart disease: An International VT Ablation Center Collaborative Group study. Heart Rhythm 12:1997–2007.
    OpenUrlPubMed
  8. ↵
    1. Stevenson W.G.,
    2. Friedman P.L.,
    3. Sager P.T.,
    4. et al.
    (1997) Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping. J Am Coll Cardiol 29:1180–1189.
    OpenUrlFREE Full Text
  9. ↵
    1. Stevenson W.G.,
    2. Sager P.T.,
    3. Natterson P.D.,
    4. Saxon L.A.,
    5. Middlekauff H.R.,
    6. Wiener I.
    (1995) Relation of pace mapping QRS configuration and conduction delay to ventricular tachycardia reentry circuits in human infarct scars. J Am Coll Cardiol 26:481–488.
    OpenUrlFREE Full Text
  10. ↵
    1. Arenal A.,
    2. Glez-Torrecilla E.,
    3. Ortiz M.,
    4. et al.
    (2003) Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease. J Am Coll Cardiol 41:81–92.
    OpenUrlFREE Full Text
  11. ↵
    1. Jais P.,
    2. Maury P.,
    3. Khairy P.,
    4. et al.
    (2012) Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia. Circulation 125:2184–2196.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Aliot E.M.,
    2. Stevenson W.G.,
    3. Almendral-Garrote J.M.,
    4. et al.
    (2009) EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 6:886–933.
    OpenUrlCrossRefPubMed
  13. ↵
    1. Gray R.J.
    (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1141–1154.
    OpenUrlCrossRef
  14. ↵
    1. Carbucicchio C.,
    2. Santamaria M.,
    3. Trevisi N.,
    4. et al.
    (2008) Catheter ablation for the treatment of electrical storm in patients with implantable cardioverter-defibrillators: short- and long-term outcomes in a prospective single-center study. Circulation 117:462–469.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Sapp J.L.,
    2. Wells G.A.,
    3. Parkash R.,
    4. et al.
    (2016) Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med 375:111–121.
    OpenUrl
  16. ↵
    1. Reddy V.Y.,
    2. Reynolds M.R.,
    3. Neuzil P.,
    4. et al.
    (2007) Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med 357:2657–2665.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Della Bella P.,
    2. Brugada J.,
    3. Zeppenfeld K.,
    4. et al.
    (2011) Epicardial ablation for ventricular tachycardia: a European multicenter study. Circ Arrhythm Electrophysiol 4:653–659.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Muser D.,
    2. Santangeli P.,
    3. Castro S.A.,
    4. et al.
    (2016) Long-term outcome after catheter ablation of ventricular tachycardia in patients with nonischemic dilated cardiomyopathy. Circ Arrhythm Electrophysiol 9:e004328.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Goya M.,
    2. Fukunaga M.,
    3. Hiroshima K.,
    4. et al.
    (2015) Long-term outcomes of catheter ablation of ventricular tachycardia in patients with structural heart disease. J Arrhythm 31:22–28.
    OpenUrl
  20. ↵
    1. Santangeli P.,
    2. Zado E.S.,
    3. Supple G.E.,
    4. et al.
    (2015) Long-term outcome with catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol 8:1413–1421.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Kumar S.,
    2. Barbhaiya C.,
    3. Nagashima K.,
    4. et al.
    (2015) Ventricular tachycardia in cardiac sarcoidosis: characterization of ventricular substrate and outcomes of catheter ablation. Circ Arrhythm Electrophysiol 8:87–93.
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Santangeli P.,
    2. Di Biase L.,
    3. Lakkireddy D.,
    4. et al.
    (2010) Radiofrequency catheter ablation of ventricular arrhythmias in patients with hypertrophic cardiomyopathy: safety and feasibility. Heart Rhythm 7:1036–1042.
    OpenUrlCrossRefPubMed
  23. ↵
    1. Dukkipati S.R.,
    2. d'Avila A.,
    3. Soejima K.,
    4. et al.
    (2011) Long-term outcomes of combined epicardial and endocardial ablation of monomorphic ventricular tachycardia related to hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol 4:185–194.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Inada K.,
    2. Seiler J.,
    3. Roberts-Thomson K.C.,
    4. et al.
    (2011) Substrate characterization and catheter ablation for monomorphic ventricular tachycardia in patients with apical hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol 22:41–48.
    OpenUrlCrossRefPubMed
  25. ↵
    1. Tholakanahalli V.N.,
    2. Bertog S.,
    3. Roukoz H.,
    4. Shivkumar K.
    (2013) Catheter ablation of ventricular tachycardia using intracoronary wire mapping and coil embolization: description of a new technique. Heart Rhythm 10:292–296.
    OpenUrlCrossRefPubMed
  26. ↵
    1. Nguyen D.T.,
    2. Tzou W.S.,
    3. Brunnquell M.,
    4. et al.
    (2016) Clinical and biophysical evaluation of variable bipolar configurations during radiofrequency ablation for treatment of ventricular arrhythmias. Heart Rhythm 13:2161–2171.
    OpenUrl
  27. ↵
    1. Kreidieh B.,
    2. Rodriguez-Manero M.,
    3. Schurmann P.,
    4. Ibarra-Cortez S.H.,
    5. Dave A.S.,
    6. Valderrabano M.
    (2016) Retrograde coronary venous ethanol infusion for ablation of refractory ventricular tachycardia. Circ Arrhythm Electrophysiol 9:e004352.
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. Piers S.R.,
    2. Tao Q.,
    3. van Huls van Taxis C.F.,
    4. Schalij M.J.,
    5. van der Geest R.J.,
    6. Zeppenfeld K.
    (2013) Contrast-enhanced MRI-derived scar patterns and associated ventricular tachycardias in nonischemic cardiomyopathy: implications for the ablation strategy. Circ Arrhythm Electrophysiol 6:875–883.
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. van Huls van Taxis C.F.,
    2. Wijnmaalen A.P.,
    3. Piers S.R.,
    4. van der Geest R.J.,
    5. Schalij M.J.,
    6. Zeppenfeld K.
    (2013) Real-time integration of MDCT-derived coronary anatomy and epicardial fat: impact on epicardial electroanatomic mapping and ablation for ventricular arrhythmias. J Am Coll Cardiol Img 6:42–52.
    OpenUrl
  30. ↵
    1. Maccabelli G.,
    2. Tsiachris D.,
    3. Silberbauer J.,
    4. et al.
    (2014) Imaging and epicardial substrate ablation of ventricular tachycardia in patients late after myocarditis. Europace 16:1363–1372.
    OpenUrlCrossRefPubMed
  31. ↵
    1. Berte B.,
    2. Sacher F.,
    3. Cochet H.,
    4. et al.
    (2015) Postmyocarditis ventricular tachycardia in patients with epicardial-only scar: a specific entity requiring a specific approach. J Cardiovasc Electrophysiol 26:42–50.
    OpenUrlCrossRefPubMed
  32. ↵
    1. Garcia F.C.,
    2. Bazan V.,
    3. Zado E.S.,
    4. Ren J.F.,
    5. Marchlinski F.E.
    (2009) Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Circulation 120:366–375.
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Bai R.,
    2. Di Biase L.,
    3. Shivkumar K.,
    4. et al.
    (2011) Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation. Circ Arrhythm Electrophysiol 4:478–485.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Philips B.,
    2. Madhavan S.,
    3. James C.,
    4. et al.
    (2012) Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Arrhythm Electrophysiol 5:499–505.
    OpenUrlAbstract/FREE Full Text
  35. ↵
    1. Vasaiwala S.C.,
    2. Finn C.,
    3. Delpriore J.,
    4. et al.
    (2009) Prospective study of cardiac sarcoid mimicking arrhythmogenic right ventricular dysplasia. J Cardiovasc Electrophysiol 20:473–476.
    OpenUrlCrossRefPubMed
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